Initiation and maintenance of optimal immune responses are triggered by engagement of the T cell receptor with its cognate MHC/peptide ligand and by the engagement of costimulatory molecules such as CD28 by its ligands CD80 (B7.1) and CD86 (B7.2). Following TCR-mediated signal, ligation of CD28 results in upregulation of interleukin-2 receptor (IL-2R) chains, increase IL-2 mRNA transcription and T cell proliferation. The objective of this research is to determine the roles that the IL-2 receptor and the costimulatory ligands B7.1 and B7.2 may play in regulating the in vitro blastogenic responses of peripheral blood mononuclear cells (PBMC) from rhesus monkeys with Borrelia burgdorferi infection to heat-killed spirochetes. PBMC response to Concanavalin A (Con A) was used as a positive control and that to media as a negative control. RNA from PBMC that had or had not been exposed to heat-killed spirochetes or to Con A was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for the expression of the B7.1 and B7.2 gene transcripts. Heat-killed spirochetes induced marginal transcription of B7.1 in PBMC from 4 of 9 animals (fold increase of 3 to 5 over unstimulated cultures). Levels of mRNA for the B7.1 ligand in Con A-induced PBMC were high and not different between animals (fold increase of 10 to 40 over unstimulated cultures). B7.2 mRNA gene transcript levels were constitutively expressed in PBMC from all monkeys and did not change upon stimulation with heat-killed spirochetes or with Con A. IL-2R expression on T cells that had been exposed to heat-killed spirochetes or to Con A was assessed by flow cytometry. The percentages of T cells bearing IL-2R in heat-killed spirochete cultures were similar and not different from unstimulated cultures in all animals. However, a significant increase in the percentage of IL-2R on T cells exposed to Con A was seen in all animals. These studies suggest that diminished expression of the B7.1 ligand as well as lac k of induction of IL-2R on T cells may contribute to the antigen-specific unresponsiveness of PBMC in rhesus monkeys with Lyme disease. FUNDING CDC PUBLICATIONS None